Deep-Learning-Based Screening and Ancillary Testing for Thyroid Cytopathology.

Thyroid cancer is the most common malignant endocrine tumor. The key test to assess preoperative risk of malignancy is cytologic evaluation of fine-needle aspiration biopsies (FNABs). The evaluation findings can often be indeterminate, leading to unnecessary surgery for benign post-surgical diagnoses. We have developed a deep-learning algorithm to analyze thyroid FNAB whole-slide images (WSIs). We show, on the largest reported data set of thyroid FNAB WSIs, clinical-grade performance in the screening of determinate cases and indications for its use as an ancillary test to disambiguate indeterminate cases. The algorithm screened and definitively classified 45.1% (130/288) of the WSIs as either benign or malignant with risk of malignancy rates of 2.7% and 94.7%, respectively. It reduced the number of indeterminate cases (N = 108) by reclassifying 21.3% (N = 23) as benign with a resultant risk of malignancy rate of 1.8%. Similar results were reproduced using a data set of consecutive FNABs collected during an entire calendar year, achieving clinically acceptable margins of error for thyroid FNAB classification.

Thyroid Cytopathology Cancer Diagnosis from Smartphone Images Using Machine Learning.

We examined the performance of deep learning models on the classification of thyroid fine-needle aspiration biopsies using microscope images captured in 2 ways: with a high-resolution scanner and with a mobile phone camera. Our training set consisted of images from 964 whole-slide images captured with a high-resolution scanner. Our test set consisted of 100 slides; 20 manually selected regions of interest (ROIs) from each slide were captured in 2 ways as mentioned above. Applying a baseline machine learning algorithm trained on scanner ROIs resulted in performance deterioration when applied to the smartphone ROIs (97.8% area under the receiver operating characteristic curve [AUC], CI = [95.4%, 100.0%] for scanner images vs 89.5% AUC, CI = [82.3%, 96.6%] for mobile images, P = .019). Preliminary analysis via histogram matching showed that the baseline model was overly sensitive to slight color variations in the images (specifically, to color differences between mobile and scanner images). Adding color augmentation during training reduces this sensitivity and narrows the performance gap between mobile and scanner images (97.6% AUC, CI = [95.0%, 100.0%] for scanner images vs 96.0% AUC, CI = [91.8%, 100.0%] for mobile images, P = .309), with both modalities on par with human pathologist performance (95.6% AUC, CI = [91.6%, 99.5%]) for malignancy prediction (P = .398 for pathologist vs scanner and P = .875 for pathologist vs mobile). For indeterminate cases (pathologist-assigned Bethesda category of 3, 4, or 5), color augmentations confer some improvement (88.3% AUC, CI = [73.7%, 100.0%] for the baseline model vs 96.2% AUC, CI = [90.9%, 100.0%] with color augmentations, P = .158). In addition, we found that our model's performance levels off after 15 ROIs, a promising indication that ROI data collection would not be time-consuming for our diagnostic system. Finally, we showed that the model has sensible Bethesda category (TBS) predictions (increasing risk malignancy rate with predicted TBS category, with 0% malignancy for predicted TBS 2 and 100% malignancy for TBS 6).

The effect of lateral neck dissection on complication rate for total thyroidectomy.

PURPOSE: To determine the complication profile for total thyroidectomy with and without concomitant lateral neck dissection using a large administrative database. MATERIALS AND METHODS: The IBM MarketScan® Commercial Database (2010-2014) analytic cohort was queried for patients ≥18 years or older undergoing total thyroidectomy (or equivalent procedures) from January 1, 2010 to June 30, 2014. Subgroup analysis was performed for patients undergoing concomitant unilateral and bilateral lateral neck dissection. The complication profiles were described. RESULTS: 55,204 patients underwent total thyroidectomy or equivalent procedures. Hypoparathyroidism or hypocalcemia was coded in 20.3% overall, with 4.7% having permanent hypoparathyroidism. Vocal cord paralysis was coded in 3.3% overall with permanent rate of 0.7%. Tracheotomy was performed in 0.3% of patients. 2743 underwent total thyroidectomy with concomitant unilateral lateral neck dissection, and 560 of these patients underwent bilateral lateral neck dissection. In patients undergoing unilateral lateral neck dissection, 30.5% of patients have hypoparathyroidism/hypocalcemia coded, with a permanent rate of 8.8%. Vocal cord paralysis was coded in 8.3% of patients, with a permanent rate of 1.9%. Tracheotomy was performed in 1.2% of patients. In patients undergoing bilateral lateral neck dissection, 39.6% had hypoparathyroidism/hypocalcemia coded, with a permanent rate of 10.9%. These patients had vocal cord paralysis coded in 10.2% of cases, with a permanent rate of 2.1%. Tracheotomy was performed in 2.5% of patients. CONCLUSION: The addition of unilateral and especially bilateral lateral neck dissection increases both overall and permanent complication rates for total thyroidectomy. These data may help to inform preoperative discussions with patients.

Associations between expression levels of nucleotide excision repair proteins in lymphoblastoid cells and risk of squamous cell carcinoma of the head and neck.

Squamous cell carcinoma of head and neck (SCCHN) is one of the most common malignancies worldwide, and nucleotide excision repair (NER) is involved in SCCHN susceptibility. In this analysis of 349 newly diagnosed SCCHN patients and 295 cancer-free controls, we investigated whether expression levels of eight core NER proteins were associated with risk of SCCHN. We quantified NER protein expression levels in cultured peripheral lymphocytes using a reverse-phase protein microarray. Compared with the controls, SCCHN patients had statistically significantly lower expression levels of ERCC3 and XPA (P = 0.001 and 0.001, respectively). After dividing the subjects by controls' median values of expression levels, we found a dose-dependent association between an increased risk of SCCHN and low expression levels of ERCC3 (adjusted OR, 1.75, and 95% CI: 1.26-2.42; Ptrend = 0.008) and XPA (adjusted OR, 1.88; 95% CI, 1.35-2.60; Ptrend = 0.001). We also identified a significant multiplicative interaction between smoking status and ERCC3 expression levels (P = 0.014). Finally, after integrating demographic and clinical variables, we found that the addition of ERCC3 and XPA expression levels to the model significantly improved the sensitivity of the expanded model on SCCHN risk. In conclusion, reduced protein expression levels of ERCC3 and XPA were associated with an increased risk of SCCHN. However, these results need to be confirmed in additional large studies.

Does the number of sentinel lymph nodes removed affect the false negative rate for head and neck melanoma?

BACKGROUND AND OBJECTIVES: Head and neck (HN) cutaneous melanoma is associated with worse disease-free survival compared to non-HN cutaneous melanoma, possibly due to inadequate staging. We aim to determine if a higher yield of sentinel lymph nodes (SLNs) affected rates of sentinel lymph node biopsy (SLNB) positivity. METHODS: Two Cancer Registries were used to identify patients who underwent SLNB for HN melanoma. A false negative (FN) was defined by nodal recurrence after negative SLNB. RESULTS: Out of 333 patients who underwent SLNB, 20% (n = 69) had a positive SLN with a FN rate of 6.3%. Those with three or more SLNs had a higher rate of SLN positivity (23.8% [17.5-29.9% CI] vs 16.4% [10.7-23.6% CI]), a lower FN rate (16.7% [10.2-21.2% CI] vs 35.3% [27.1-42.9% CI]), and higher sensitivity (83.3% [82.59-84.09% CI] vs 65.7% [64.87-66.53% CI]) compared to those with one or two SLNs. Of patients in Group 1 (one or two SLNs) with a positive SLN who underwent completion lymph node dissection (20/23), 47% (33-61% CI) had one or more positive non-sentinel nodes compared to 29% (16-51%) of patients in Group 2 (three or more SLNs) (42/46). CONCLUSION: In HN melanoma cases in which multiple nodes are identified, removal of all SLNs will more adequately stage patients.

[(99m)Tc]Tilmanocept Accurately Detects Sentinel Lymph Nodes and Predicts Node Pathology Status in Patients with Oral Squamous Cell Carcinoma of the Head and Neck: Results of a Phase III Multi-institutional Trial.

BACKGROUND: [(99m)Tc]Tilmanocept, a novel CD206 receptor-targeted radiopharmaceutical, was evaluated in an open-label, phase III trial to determine the false negative rate (FNR) of sentinel lymph node biopsy (SLNB) relative to the pathologic nodal status in patients with intraoral or cutaneous head and neck squamous cell carcinoma (HNSCC) undergoing tumor resection, SLNB, and planned elective neck dissection (END). Negative predictive value (NPV), overall accuracy of SLNB, and the impact of radiopharmaceutical injection timing relative to surgery were assessed. METHODS AND FINDINGS: This multicenter, non-randomized, single-arm trial (ClinicalTrials.gov identifier NCT00911326) enrolled 101 patients with T1-T4, N0, and M0 HNSCC. Patients received 50 µg [(99m)Tc]tilmanocept radiolabeled with either 0.5 mCi (same day) or 2.0 mCi (next day), followed by lymphoscintigraphy, SLNB, and END. All excised tissues were evaluated for tissue type and tumor presence. [(99m)Tc]Tilmanocept identified one or more SLNs in 81 of 83 patients (97.6 %). Of 39 patients identified with any tumor-positive nodes (SLN or non-SLN), one patient had a single tumor-positive non-SLN in whom all SLNs were tumor-negative, yielding an FNR of 2.56 %; NPV was 97.8 % and overall accuracy was 98.8 %. No significant differences were observed between same-day and next-day procedures. CONCLUSIONS: Use of receptor-targeted [(99m)Tc]tilmanocept for lymphatic mapping allows for a high rate of SLN identification in patients with intraoral and cutaneous HNSCC. SLNB employing [(99m)Tc]tilmanocept accurately predicts the pathologic nodal status of intraoral HNSCC patients with low FNR, high NPV, and high overall accuracy. The use of [(99m)Tc]tilmanocept for SLNB in select patients may be appropriate and may obviate the need to perform more extensive procedures such as END.

Epiglottic cyst causing dysphagia and impending airway obstruction.

Laryngeal cysts are relatively rare benign lesions of the larynx. Congenital cysts can cause neonatal respiratory distress and death, but airway obstruction due to acquired cysts in adults is rare. We present a case report of 51-year-old male with dysphagia who was found to have a mobile pedunculated epiglottic cyst that intermittently caused partial obstruction of the laryngeal inlet. Patient was taken to operating room and following transoral fiberoptic intubation, endoscopic excision of this cyst was accomplished. Patient's postoperative course was uneventful.

Leukotriene C4 induces migration of human monocyte-derived dendritic cells without loss of immunostimulatory function.

Generation of human monocyte-derived dendritic cells (DCs) for cancer vaccination involves ex vivo maturation in the presence of proinflammatory cytokines and prostaglandin E(2) (PGE(2)). Although the inclusion of PGE(2) during maturation is imperative for the induction of DC migration, PGE(2) has unfavorable effects on the immunostimulatory capacity of these cells. Like PGE(2), leukotrienes (LTs) are potent mediators of DC migration. We therefore sought to characterize the migratory and immunologic properties of DCs that matured in the presence of LTB(4), LTC(4), LTD(4), and PGE(2). Here, we demonstrate that DCs matured in the presence of LTC(4), but not LTB(4) or LTD(4), are superior to PGE(2)-matured DCs in stimulating CD4(+) T-cell responses and in inducing antigen-specific cytotoxic T lymphocytes (CTLs) in vitro without concomitant induction or recruitment of regulatory T cells (Tregs). LTC(4)-matured DCs migrate efficiently through layers of extracellular matrix and secrete higher levels of immunostimulatory IL-12p70 while producing reduced levels of immune-inhibitory IL-10, IL12p40, indoleamine-2,3-dioxidase, and TIMP-1 (tissue inhibitor of matrix metalloproteinases). Intracellular calcium mobilization and receptor antagonist studies reveal that, in contrast to LTD(4), LTC(4) did not signal through CysLTR(1) in DCs. Collectively, our data suggest that LTC(4) represents a promising candidate to replace PGE(2) in DC maturation protocols for cancer vaccination.

FoxP3 and indoleamine 2,3-dioxygenase immunoreactivity in sentinel nodes from melanoma patients.

OBJECTIVE: 1) Assess FoxP3/indoleamine 2,3-dioxygenase immunoreactivity in head and neck melanoma sentinel lymph nodes and 2) correlate FoxP3/indoleamine 2,3-dioxygenase with sentinel lymph node metastasis and clinical recurrence. STUDY DESIGN: Retrospective cohort study. METHODS: Patients with sentinel lymph node biopsy for head and neck melanoma between 2004 and 2011 were identified. FoxP3/indoleamine 2,3-dioxygenase prevalence and intensity were determined from the nodes. Poor outcome was defined as local, regional or distant recurrence. The overall immunoreactivity score was correlated with clinical recurrence and sentinel lymph node metastasis using the chi-square test for trend. RESULTS: Fifty-six sentinel lymph nodes were reviewed, with 47 negative and 9 positive for melanoma. Patients with poor outcomes had a statistically significant trend for higher immunoreactivity scores (p=0.03). Positive nodes compared to negative nodes also had a statistically significant trend for higher immunoreactivity scores (p=0.03). Among the negative nodes, there was a statistically significant trend for a poor outcome with higher immunoreactivity scores (p=0.02). CONCLUSION: FoxP3/indoleamine 2,3-dioxygenase immunoreactivity correlates with sentinel lymph node positivity and poor outcome. Even in negative nodes, higher immunoreactivity correlated with poor outcome. Therefore higher immunoreactivity may portend a worse prognosis even without metastasis in the sentinel lymph node. This could identify a subset of patients that may benefit from future trials and treatment for melanoma through Treg and IDO suppression.

Artificial Intelligence in Medicine: A Caution About Good Intentions and Where It May Lead.

Implementing Artificial Intelligence in medicine is revolutionizing how medicine is practiced. It has much promise in bringing about improved clinical outcomes and efficiency while decreasing costs. There are also concerns and unintended consequences that are being realized and significant efforts to consider ethical principles in the implementation of Artificial Intelligence in medicine. One potential consequence may be the loss of what has been described as the soul of medicine: the physician-patient relationship. This relationship is especially precious in the context of what the US Surgeon General Vivek H. Murthy MD has called an "Epidemic of Loneliness and Isolation." This commentary describes considerations and potential steps to protect this vital relationship while implementing Artificial Intelligence approaches to improving patient care. If not vigilant, Artificial Intelligence may unintentionally erode the physician-patient relationship resulting in physician/patient isolation.

Impact of anti-CD25 monoclonal antibody on dendritic cell-tumor fusion vaccine efficacy in a murine melanoma model.

BACKGROUND: A promising cancer vaccine involves the fusion of tumor cells with dendritic cells (DCs). As such, a broad spectrum of both known and unidentified tumor antigens is presented to the immune system in the context of the potent immunostimulatory capacity of DCs. Murine studies have demonstrated the efficacy of fusion immunotherapy. However the clinical impact of DC/tumor fusion vaccines has been limited, suggesting that the immunosuppresive milieu found in patients with malignancies may blunt the efficacy of cancer vaccination. Thus, novel strategies to enhance fusion vaccine efficacy are needed. Regulatory T cells (Tregs) are known to suppress anti-tumor immunity, and depletion or functional inactivation of these cells improves immunotherapy in both animal models and clinical trials. In this study, we sought to investigate whether functional inactivation of CD4+CD25+FoxP3+ Treg with anti-CD25 monoclonal antibody (mAb) PC61 prior to DC/tumor vaccination would significantly improve immunotherapy in the murine B16 melanoma model. METHODS: Treg blockade was achieved with systemic PC61 administration. This blockage was done in conjunction with DC/tumor fusion vaccine administration to treat established melanoma pulmonary metastases. Enumeration of these metastases was performed and compared between experimental groups using Wilcoxon Rank Sum Test. IFN-gamma ELISPOT assay was performed on splenocytes from treated mice. RESULTS: We demonstrate that treatment of mice with established disease using mAb PC61 and DC/tumor fusion significantly reduced counts of pulmonary metastases compared to treatment with PC61 alone (p=0.002) or treatment with control antibody plus fusion vaccine (p=0.0397). Furthermore, IFN-gamma ELISPOT analyses reveal that the increase in cancer immunity was mediated by anti-tumor specific CD4+ T-helper cells, without concomitant induction of CD8+ cytotoxic T cells. Lastly, our data provide proof of principle that combination treatment with mAb PC61 and systemic IL-12 can lower the dose of IL-12 necessary to obtain maximal therapeutic efficacy. CONCLUSIONS: To our knowledge, this is the first report investigating the effects of anti-CD25 mAb administration on DC/tumor-fusion vaccine efficacy in a murine melanoma model, and our results may aide the design of future clinical trials with enhanced therapeutic impact.

Local secretion of IL-12 augments the therapeutic impact of dendritic cell-tumor cell fusion vaccination.

BACKGROUND: The development of dendritic cell (DC)-tumor fusion vaccines is a promising approach in cancer immunotherapy. Using fusion vaccines allows a broad spectrum of known and unidentified tumor-associated antigens to be presented in the context of MHC class I and class II molecules, with potent co-stimulation provided by the DCs. Although DC-tumor fusion cells are immunogenic, murine studies have shown that effective immunotherapy requires a third signal, which can be provided by exogenous interleukin 12 (IL-12). Unfortunately, systemic administration of IL-12 induces severe toxicity in cancer patients, potentially precluding clinical use of this cytokine to augment fusion vaccine efficacy. To overcome this limitation, we developed a novel approach in which DC-tumor fusion cells locally secrete IL-12, then evaluated the effectiveness of this approach in a murine B16 melanoma model. MATERIALS AND METHODS: Tumor cells were stably transduced to secrete murine IL-12p70. These tumor cells were then electrofused to DC to form DC-tumor heterokaryons. These cells were used to treat established B16 pulmonary metastases. Enumeration of these metastases was performed and compared between experimental groups using Wilcoxon rank sum test. Interferon γ enzyme-linked immunosorbent spot assay was performed on splenocytes from treated mice. RESULTS: We show that vaccination with DCs fused to syngeneic melanoma cells that stably express murine IL-12p70 significantly reduces counts of established lung metastases in treated animals when compared with DC-tumor alone (P = 0.029). Interferon γ enzyme-linked immunosorbent spot assays suggest that this antitumor response is mediated by CD4(+) T cells, in the absence of a tumor-specific CD8(+) T cell response, and that the concomitant induction of antitumor CD4(+) and CD8(+) T cell responses required exogenous IL-12. CONCLUSIONS: This study is, to the best of our knowledge, the first report that investigates the impact of local secretion of IL-12 on antitumor immunity induced by a DC-tumor fusion cell vaccine in a melanoma model and may aid the rational design of future clinical trials.

Effectiveness of a postoperative disposition protocol for sleep apnea surgery.

PURPOSE: 1) Evaluate the effectiveness of a postoperative disposition protocol for upper airway surgery in patients with sleep apnea. 2) Compare the cost-effectiveness of outpatient and overnight observational sleep apnea surgery versus surgical intensive care admission determined by preoperative screening criteria. MATERIALS AND METHODS: A new preoperative protocol for sleep apnea surgery was instituted at the Durham Veterans Affairs Medical Center in 2008 to triage patients undergoing sleep apnea surgery to one of three postoperative dispositions: intensive care, routine ward bed, or discharge home. An Institutional Review Board approved retrospective chart review of patients undergoing sleep apnea surgery between May 2008 and January 2012 was performed. Postoperative complications and cost comparisons were assessed between each of the three postoperative disposition groups. RESULTS: 115 patients underwent sleep apnea surgery between July 2008 and January 2012. 11 patients were excluded leaving 104 patients in the final analysis. Median follow-up was 1.25months. Overall complication rate was 12.5%. Eight complications occurred in the group triaged to intensive care, and 5 occurred in those triaged to lesser levels of postoperative care. All serious complications occurred during the immediate postoperative period. Based on only room charges, $125,275 was saved over the 3.6years of this study. CONCLUSION: A post operative disposition protocol can be effectively used to triage patients to less than intensive postoperative care. In institutions like the Durham VA, where sleep apnea patients were routinely triaged to intensive care, postoperative resources will be more efficiently utilized.

International Collaboration Trends in Facial Plastic and Reconstructive Surgery: A Systematic Bibliometric Scoping Review.

Importance: Research in facial plastic and reconstructive surgery (FPRS) in the global health setting, especially in low- and middle-income countries (LMICs), is increasing year by year. As this work progresses, it will be crucial to include voices and perspectives of individuals living in the LMICs being studied. Objective: To characterize and understand international collaborations in published literature on FPRS care in a global health setting and report patterns in whether these articles included authors from the LMICs in which the studies took place. Evidence Review: A systematic bibliometric scoping review of articles in Scopus from 1971 to 2022 was performed using a set list of search terms; studies were included using predetermined inclusion and exclusion criteria. Studies met criteria for inclusion if the abstract or text contained information regarding surgeons from a different country performing surgery or conducting research in an LMIC within the domain of FPRS. Exclusion criteria were studies that did not mention a facial plastic or reconstructive surgery and studies where both an HIC and LMIC were not mentioned. Findings: A total of 286 studies met criteria for inclusion. The highest percentage of studies (n = 72, 25.2%) were conducted across multiple countries. A total of 120 studies (41.9%) discussed cleft lip/palate. Overall, 141 studies (49.5%) included at least 1 author from the host LMIC; 89 (31.1%) had first authors from LMICs, and 72 (25.2%) had senior authors from LMICs. A total of 79 studies (27.6%) described humanitarian clinical service trips without mentioning research or education in the text. The remaining studies described research, education projects, or a combination. The published literature on humanitarian service trips had the lowest rate of inclusion of a first or senior author from the host LMICs. Conclusions and Relevance: In this systematic bibliometric scoping review, findings showed a general trend of increased international work in the field of FPRS. However, there continues to be a paucity of inclusive authorship trends, with the majority of studies not including first or senior authors from LMICs. The findings presented here encourage new collaborations worldwide, as well as the improvement of existing efforts.

Octreotide may improve pharyngocutaneous fistula healing through downregulation of cystatins: A pilot study.

Background: Pharyngocutaneous fistula (PCF) and salivary leaks are well known complications of head and neck surgery. The medical management of PCF has included the use of octreotide without a well-defined understanding of its therapeutic mechanism. We hypothesized that octreotide induces alterations in the saliva proteome and that these alterations may provide insight into the mechanism of action underlying improved PCF healing. We undertook an exploratory pilot study in healthy controls that involved collecting saliva before and after a subcutaneous injection of octreotide and performing proteomic analysis to determine the effects of octreotide. Methods: Four healthy adult participants provided saliva samples before and after subcutaneous injection of octreotide. A mass-spectrometry based workflow optimized for the quantitative proteomic analysis of biofluids was then employed to analyze changes in salivary protein abundance after octreotide administration. Results: There were 3076 human, 332 Streptococcus mitis, 102 G. haemolyans, and 42 Granulicatella adiacens protein groups quantified in saliva samples. A paired statistical analysis was performed using the generalized linear model (glm) function in edgeR. There were and ~300 proteins that had a p < .05 between the pre- and post-octreotide groups ~50 proteins with an FDR-corrected p < .05 between pre- and post-groups. These results were visualized using a volcano plot after filtering on proteins quantified by 2 more or unique precursors. Both human and bacterial proteins were among the proteins altered by octreotide treatment. Notably, four isoforms of the human cystatins, belonging to a family of cysteine proteases, that had significantly lower abundance after treatment. Conclusion: This pilot study demonstrated octreotide-induced downregulation of cystatins. By downregulation of cystatins in the saliva, there is decreased inhibition of cysteine proteases such as Cathepsin S. This results in increased cysteine protease activity that has been linked to enhanced angiogenic response, cell proliferation and migration that have resulted in improved wound healing. These insights provide first steps at furthering our understanding of octreotide's effects on saliva and reports of improved PCF healing.

Lateral neck dissection surgeon volume and complications in head and neck endocrine malignancy.

Background: Increased surgeon volume is associated with decreased complications for many surgeries, including thyroidectomy. We sought to use two national databases to assess for associations between surgeon volume and complications in patients undergoing lateral neck dissection for thyroid or parathyroid malignancy. Methods: Lateral neck dissections for thyroid and parathyroid cancer from the Nationwide Inpatient Sample and State Inpatient Database were analyzed. The primary outcome was any inpatient complication common to thyroidectomy, parathyroidectomy, or lateral neck dissection. The principle independent variable was surgeon volume. Multivariable analysis was then performed on this retrospective cohort study. Results: The 1,094 Nationwide Inpatient Sample discharges had a 28% (305/1,094) complication rate. After adjustment, surgeons with volumes between 3-34 neck dissections/year demonstrated a surgeon volume-complication rate association [adjusted odds ratio: 1.03; 95% confidence interval (CI): 1.01-1.05]. The 1,235 State inpatient Database discharges had a 21% (258/1,235) overall complication rate, and no association between surgeon volume and complication rates (P=0.25). Conclusions: This retrospective review of 2,329 discharges for patients undergoing lateral neck dissection for thyroid or parathyroidectomy demonstrated somewhat conflicting results. The Nationwide Inpatient Sample demonstrated increasing complication rates for increasing surgeon volume among intermediate volume surgeons, while the State Inpatient Database demonstrated no surgeon volume-complication association. Given these disparate results, and further limitations with these databases, conclusions regarding surgical volume and clinical decision making based on these data should be assessed cautiously.

A Clinical Study to Assess Diffuse Reflectance Spectroscopy with an Auto-Calibrated, Pressure-Sensing Optical Probe in Head and Neck Cancer.

Diffuse reflectance spectroscopy (DRS) is a powerful tool for quantifying optical and physiological tissue properties such as hemoglobin oxygen saturation and vascularity. DRS is increasingly used clinically for distinguishing cancerous lesions from normal tissue. However, its widespread clinical acceptance is still limited due to uncontrolled probe-tissue interface pressure that influences reproducibility and introduces operator-dependent results. In this clinical study, we assessed and validated a pressure-sensing and automatic self-calibration DRS in patients with suspected head and neck squamous cell carcinoma (HNSCC). The clinical study enrolled nineteen patients undergoing HNSCC surgical biopsy procedures. Patients consented to evaluation of this improved DRS system during surgery. For each patient, we obtained 10 repeated measurements on one tumor site and one distant normal location. Using a Monte Carlo-based model, we extracted the hemoglobin saturation data along with total hemoglobin content and scattering properties. A total of twelve cancer tissue samples from HNSCC patients and fourteen normal tissues were analyzed. A linear mixed effects model tested for significance between repeated measurements and compared tumor versus normal tissue. These results demonstrate that cancerous tissues have a significantly lower hemoglobin saturation compared to normal controls (p < 0.001), which may be reflective of tumor hypoxia. In addition, there were minimal changes over time upon probe placement and repeated measurement, indicating that the pressure-induced changes were minimal and repeated measurements did not differ significantly from the initial value. This study demonstrates the feasibility of conducting optical spectroscopy measurements on intact lesions prior to removal during HNSCC procedures, and established that this probe provides diagnostically-relevant physiologic information that may impact further treatment.

Bilateral renal cell carcinoma metastasis in the oral cavity.

Cancer metastases to the oral cavity are reported infrequently. Renal cell carcinoma has a high metastatic potential, with approximately one third of patients presenting with metastatic disease. New lesions in the oral cavity often rely on preoperative biopsy to establish the diagnosis. However, we report an unusual case in a setting of known renal cell carcinoma disease, where initial pathology and culture data were misleading. Appropriate follow-up and a high index of suspicion will remain necessary. Surgical excision is the treatment of choice.

Dendritic cell-tumor cell fusion vaccines.

The use of cell fusion has been applied to the development of immunotherapy cancer vaccines. This has typically involved the fusion of dendritic cells and tumor cells. The resultant hybrid uses the specialized antigen presentation properties supplied by the dendritic cell fusion partner to present tumor antigens, both known and yet undefined, to the immune system. This chapter critically examines the scientific foundation of this approach mainly focusing on studies over the last decade. This will include basic principles of tumor fusion vaccines, summary of pre-clinical and clinical data, concluding with remaining challenges and directions.

Head and neck cancer research collaborations between the United States and low- and middle-income countries: 10-year publication analysis.

BACKGROUND: Disparities exist for head and neck cancer (HNC) patients between those in developed countries and low- and middle-income countries (LMICs). To improve HNC care globally, collaborations between the United States and LMICs have been established. Our objectives are: (1) define trends of collaborative HNC publications among LMICs and the United States and (2) assess the global distribution of these publications by region. METHODS: A Scopus search identified all HNC research publications during 2009 to 2018. These were then categorized by type (basic vs. clinical) and by global regions. RESULTS: Five thousand one hundred and seventy collaborative publications were identified, of which 41% were basic science and 59% clinical. The highest rate of collaborative publications for both basic science and clinical papers was seen in the East Asia/Pacific region. CONCLUSIONS: The number of collaborative research publications per year in HNC is increasing across the globe, at varying rates in different global regions.